Lactic acid bacteria are abundantly present in fermented foods such as Kimchi and usually dwell in the digestive tract, functioning to degrade fibroid materials and composite proteins into useful metabolites. As such, live microorganisms that confer a health benefit on the host by improving the microbial environment in the gut are generally called probiotics. To function as probiotics after oral uptake, microorganisms must reach the intestine alive and must stay on intestinal surfaces. Therefore, they are fundamentally required to have a tolerance to acid and bile acid and an ability to adhere to intestinal epithelial cells.
Representative among probiotics are Lactobacillus sp. microorganisms, which are abundantly present in Korean conventional fermented foods such as Kimchi. Lactobacillus sp. microorganisms are homo- or hetero-fermentative lactic acid bacilli which can be readily found in human and animal guts or in the fermentation process of diary products or vegetables. Lactobacillus sp. microorganisms are known to have the beneficial functions of vitamin synthesis, anticancer activity and blood cholesterol reduction in addition to maintaining the intestines at an acidic pH that inhibits the excessive growth of harmful bacteria, such as E. coli, or Clostridium and improving diarrhea and constipation. Acidophilin, produced by fermenting lactic acid bacilli, can act like an antibiotic and inhibit the growth of dysentery bacilli, salmonella, staphylococci, E. coli, etc. Reportedly, this natural antibiotic can bind the bowel by suppressing the growth of diarrhea-causing bacteria and normalizing the intestinal microfloral environment (Michael and Philippe, Probiotics and prebiotics: Effects on diarrhea, The journal of nutrition, Volume 137, March 2007, pages 803S-811S; Roberfroid, Prebiotics and probiotics: Are they functional foods?, American journal of clinical nutrition, Volume 71, June 2000, pages 1682S-1687S).
Active research has been made to take advantage of Lactobacillus sp. microorganisms in the development of probiotic agents and animal feeds. Bacterial diarrhea causes livestock to lose weight or even die. To increase livestock production by preventing the onset of diseases, antibiotics have been generally added to the feedstock of livestock. However, because the use of antibiotics causes the advent of resistant bacteria and a residuum of antibiotics within livestock products, it is regulated by law and therefore, and organic methods of raising livestock have been recommended (Korean Patent Laid-Open Publication No. 1998-78358)(McEwen and Fedorka-Cray, Antimicrobial use and resistance in animals, Clinical infectious Diseases, Volume 34, June 2002, pages S93-S106).
In addition, lactic acid bacteria such as Lactobacillus sp. microorganisms are known to exhibit immunopotentiating activity. With the aggravation of environmental pollution in the world and the increased uptake of instant food, allergy and atopic diseases associated with abnormal immunomodulation have been increased rapidly over the world including Korea. In Europe, keen attention has been paid to bacteriotherapy in which pathogenic microorganisms are displaced with beneficial bacteria by the oral administration of, for example, lactic acid bacteria, thereby treating or alleviating diseases.
A report has it that the administration of Lactobacillus rhamnosus GG has reduced the onset of atopic diseases in infants to half the level (Kalliomaki et. al., Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial, Lancet, Volume 357, April 2001, pages 1076-1079). Also, children with atopic dermatitis were reported to undergo a decrease in both the area and extent of dermatitis when they were administered with Lactobacillus rhamnosus and L. reuteri (Rosenfeldt et. al., Effect of probiotic Lactobacillus strains in children with atopic dermatitis, Dermatologic and ocular diseases, Volume 111, February 2003, pages 389-395).
The immunopotentiating mechanism of lactic acid bacteria has been steadily researched and has yet to be proven. It is generally inferred that after being introduced via an oral route, lactic acid bacteria settle down and inhabit the gut, positively affecting the intestinal immune system. For example, the uptake of lactic acid bacteria with yogurt is reported to increase the antibacterial activity of Peyer's patch's lymphocytes. Tests with animals and humans showed that lactic acid bacteria potentiate the response of IgA. Further, lactic acid bacteria have an influence on both innate immunity and adaptive immunity. In the intestinal immune system, the cells imparting innate immunity defend the host from infection of pathogens by recognizing and killing them. In adaptive immunity, macrophages, which plays a role in phagocytosing pathogens and presenting antigens, are activated to stimulate the production of various cytokines, inter alia, IL12 and IL-18. In this regard, some of the constituents of the cell wall of lactic acid bacteria are known to activate the NF-κB and STAT signaling pathway in macrophages and thereby stimulate the production of cytokines. In addition lactic acid bacteria increase the production of IL-12, IL-18, and TNF-α in dendritic cells, which are specialized antigen-presenting cells abundantly found in the lymph nodes and the mucous membranes of the digestive tract, as well as the expression of T-lymphocyte activating surface molecules such as MHC class II and B7-2 (Cross et. al., Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria?, International Immunopharmacology, Volume 1, May 2001, pages 891-901).
T lymphocytes play a central role in adaptive immunity. There is a Th1 response leading to cell-mediated immunity and also a Th2 response leading to humoral immunity in the adaptive immunity. The cytokines produced by antigen-presenting cells differ between the Th1 response to Th2 response. IL-12, IL-18, and interferon (IFN) are predominantly produced in the Th1 response whereas the Th2 response predominantly results in the production of PGE2, IL-4, and IL-10. For immune system homeostasis, there must be an appropriate balance between the Th1 and Th2 responses. The disruption of Th1/Th2 balance gives rise to immune-mediated diseases. Generally, Th1 cells are more effective against infection, while Th2 cells are responsible mainly for allergic and inflammatory responses. When acting normally, Th2 cells protect the body from dust and other undesired substances. When excessively activated, Th2 cells induce the hyperproduction of IgE antibodies, giving rise to allergic reactions to proteins which are not normally antigenic (e.g., pollen, foods). Th1 responses must be in balance with Th2 responses. A surplus or deficiency of either of them causes diseases. Chronic stress induces the continuous release of cortisol, which causes a decrease in Th2 response but an increase in Th1 response, resulting in the induction of cancer, atopy, allergy, and autoimmune diseases (Elenkov and Chrousos, Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease, Trends in Endocrinology and Metabolism, Volume 10, November 1999, pages 359-368).
Lactic acid bacteria stimulate the production of the Th1 cytokine IFN-γ, but suppress the release of the Th2 cytokines IL-4 and IL-5 in T lymphocytes, as shown in an in vivo experiment (Matsuzaki et. al., The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice, Journal of Dairy Science, Volume 81, January 1998, pages 48-53). Another experiment exhibited that when ovalbumin-primed mice that showed a Th2 bias were administered orally with lactic acid bacteria, the IFN-γ level of the splenocytes increased but the IL-4, IL-5 and IgE levels decreased and that incubating the splenocytes isolated from ovalbumin-primed mice with a Th2 bias, together with lactic acid bacteria, brought about a change in cytokine and IgE levels in agreement with the results of the oral administration experiment. However, because the incubation of only T lymphocytes together with lactic acid bacteria did not lead to a significant increase in IFN-γ level, T lymphocytes are thought to require antigen-presenting cells such as macrophages and dendritic cells for their IFN-γ production (Kato et. al., Lactic acid bacterium potently induces the production of interleukin-12 and interferon-gamma by mouse splenocytes, International Journal of Immunopharmacology, Volume 21, February 1999, pages 121-131). IL-12 and IL-18, which are cytokines playing an important role in differentiating Th0 lymphocytes into Th1 lymphocytes, are produced in macrophages or dendritic cells. When treated with lactic acid bacteria, splenocytes or microphages are known to increase the production of IL-12, IL-18 and IFN-α in dose-dependent manners. As such, lactic acid bacteria increases the production of IL-12, IL-18 and IFN-α in macrophages, thus promoting differentiation into Th1 cells with the concomitant induction of IFN-γ production, so that they can act to drive a Th2-predominant condition toward a Th1/Th2 balance (Cross et. al., Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria?, International Immunopharmacology?, Volume 1, May 2001, pages 891-901). Therefore, lactic acid bacteria are reported to be useful in the prevention or treatment of immune-mediated diseases such as cancers, atopy, allergy and autoimmune diseases, which are caused by the disruption of the Th1/Th2 balance triggered by an excessive Th2 response.